JP2000239388A - Mercapto group-bearing silicic compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject new compound consisting of a specific silicic compound and useful as an adsorbent for amino acids, peptides, proteins, etc. SOLUTION: This compound is a compound having a partial structure of formula I (R1 to R4 are each O-Si, a group OR5 (R5 is H or a 1-4C alkyl) or the like), and is obtained by condensation reaction between a compound of formula II [R1' to R4' are each OH, a halogen, group of OR5' (R5' is H or a 1-4C alkyl) or the like] and a compound of formula III [R6 to R9 are each OH, a halogen, group of O-R10 (R10 is a 1-4C alkyl) or the like] in the weight ratio of pref. (40:60) to (70:30); wherein the above reaction is carried out pref. as follows: a dealcoholization reaction is made in the presence of an acid catalyst and then dehydration condensation reaction is made in the presence of a basic catalyst. An absorbent consisting of this compound can be used as a support for column chromatography intended for separation and can also be used for eliminating antigen proteins including allergens.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a silicon compound useful for the adsorption of amino acids, peptides, proteins and the like.

[0002]

2. Description of the Related Art Proteins constitute an important part of the body, and are the main constituents of various life phenomena such as enzymes, and are vital components along with peptides and amino acids, which are the partial structures. Therefore, to understand life phenomena,
It is important to know these characteristics and structure, as well as their distribution. Therefore, development of means for separating these amino acids, peptides, proteins and the like has been desired. From such a viewpoint, bile bodies for separation in which amino groups were introduced into silica gel and gel filtration carriers have been developed and used as separation carriers. There is a limit in the performance, and further, there has been a demand for a separation carrier having a different mechanism, which has excellent adsorptivity.

From another viewpoint, peptides and proteins not only have a physiologically active effect, but also may have an unfavorable effect on the living body such as, for example, allergens. There are many things that need to be removed. At present, methods for removing such peptides and proteins include a method using an ion-exchange resin and a dialysis method using a semi-permeable membrane, but if the ion-exchange resin is ionized, All of them are adsorbed, and a semi-permeable membrane requires a high pressure and a solvent, so it cannot be said that such a removing means is practical. That is, there has been a demand for the development of these removing means using a protein / peptide adsorbent caused by a novel mechanism.

On the other hand, a silicon compound having a partial structure represented by the following general formula (I) is a novel compound unknown in the literature,
Therefore, it has not been known at all that such a silicon compound is excellent in the ability to adsorb amino acids, peptides, proteins and the like.

[0005]

DISCLOSURE OF THE INVENTION The present invention has been made under such circumstances, and has a novel amino acid, peptide,
An object of the present invention is to provide an adsorbent such as a protein.

[0006]

In view of such a situation, the present inventors have conducted intensive research efforts to find novel adsorbents such as amino acids, peptides, and proteins, and as a result, the following general formula (I) has been obtained. Such action was found in a silicate compound having the represented partial structure, and the invention was completed. Hereinafter, the present invention will be described in detail focusing on embodiments.

[0007]

Embedded image Formula (I) (wherein, R1, R2, R3 and R4 each independently represent O-Si, OR5, R5, and R5 each independently represents a carbon atom which may have a hydrogen atom or a mercapto group. Represents an alkyl group of the formulas 1 to 4, and R1, R2, R3
Alternatively, at least one of R4 is an alkyl group having 1 to 4 carbon atoms having a mercapto group. )

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Silicon compound of the present invention The silicon compound of the present invention has a partial structure represented by the above general formula (I). As a method for producing such a silicon compound, 1) a silica is reacted with a silane coupling agent represented by the general formula (IV) to perform a surface treatment. 2) A silane coupling agent represented by the general formula (IV) is reacted with silicones such as dimethicone, methylsiloxane network polymer and cross-linked dimethylpolysiloxane to silylate hydroxyl groups. 3) Condensing the silicon compound represented by the general formula (II) with the compound represented by the general formula (III). Can be exemplified, and any of these can be used. The most preferred of these production methods is the method 3). This is because a mercaptoalkyl group which is responsible for the adsorption ability of proteins and the like, which is the gist of the present invention, can be introduced uniformly and in large amounts. The raw materials used in these production methods are already commercially available, and there is no difficulty in obtaining them. Each of these reactions can be carried out in the presence or absence of a catalyst such as an acid or an alkali. In the cases 1) and 2), the silicone is heated to 100 to 200 ° C. under no catalyst conditions. Selected from the compounds of the general formula (IV) for silica and silica
It is preferable to react 1 to 40% by weight of a kind or two or more kinds. The reaction temperature may be set according to the boiling points and reactivity of these raw materials. In the case of 3), it is particularly preferable to carry out a dealcoholization reaction by adding an acid catalyst, followed by dehydration-condensation using a base catalyst since uniform properties can be obtained. At this time, the ratio of the compound represented by the general formula (II) to the compound represented by the general formula (III) is preferably from 40:60 to 70:30 from the viewpoint of physical properties. These silicon compounds of the present invention can be obtained in the form of a liquid to a solid. However, when used as the adsorbent of the present invention, it is particularly preferable that the silicon compound is a solid in terms of its operability.

[0009]

Embedded image Formula (II) (wherein, R1 ′, R2 ′, R3 ′ and R4 ′ each independently represent OH, a halogen atom, OR5 ′, R5 ′, and R5 ′ each independently represents a hydrogen atom or a mercapto group. Represents an alkyl group having 1 to 4 carbon atoms which may have the formula, and at least one of R 1 ′, R 2 ′, R 3 ′ or R 4 ′ is an alkyl group having 1 to 4 carbon atoms having a mercapto group. And at least one is an alkyloxy group having 1 to 4 carbon atoms or a halogen atom.)

[0010]

Embedded image General formula (III) (wherein, R6, R7, R8 and R9 each independently represent OH, a halogen atom, O-R10 or R10, R10 represents an alkyl group having 1 to 4 carbon atoms, and R6,
At least two of R7, R8 and R9 are a hydroxyl group, an alkyloxy group or a halogen atom. )

[0011]

Embedded image Formula (IV) (wherein, R11, R12, R13, and R14 each independently represent a halogen atom, a group represented by OR15, R
R15 represents an alkyl group having 1 to 4 carbon atoms which may have a mercapto group;
At least one of 1, R12, R13 and R14 is a mercaptoalkyl group, and at least one is an alkyloxy group or a halogen atom. )

(2) Action of the Compound of the Present Invention The silicon compound of the present invention has an excellent ability to adsorb amino acids, peptides, proteins, and the like, as shown in Examples described later. The adsorbents of the present invention such as amino acids, peptides and proteins comprise such silicon compounds of the present invention. Therefore, the adsorbent of the present invention can be used as a carrier for column chromatography by utilizing this property and used for separation thereof. Further, it can be used to remove antigen proteins such as allergens by utilizing this adsorption capacity. Such removal may be achieved by packing the mixture in a column chromatography or the like, and flowing a liquid containing the protein or the like to be removed into the column. Further, as an innovative use, the silicon compound of the present invention is used in cosmetics and the like, hydrocarbons such as petrolatum and microcrystalline wax, esters such as jojoba oil and gay wax, and triglycerides such as beef tallow and olive oil. , Higher alcohols such as cetanol and oleyl alcohol, fatty acids such as stearic acid and oleic acid, polyhydric alcohols such as glycerin and 1,3-butanediol, nonionic surfactants, anionic surfactants and cationic surfactants Agents, amphoteric surfactants, thickeners such as ethanol and carbopol, preservatives, ultraviolet absorbers, antioxidants, dyes, powders, etc. It can also remove allergens from it and alleviate hay fever and the like. In this case, the content of the silicon compound of the present invention in the cosmetic is preferably 1 to 50% by weight. This is because such an effect does not appear when the amount is too small, and the effect reaches a plateau when the amount is too large, and the degree of freedom of many components may be impaired. All such uses fall within the technical scope of the present invention.

[0013]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the present invention is not limited to only these Examples.

Example 1 According to the following method, a silicon compound as an adsorbent for amino acids, peptides and proteins of the present invention was obtained. That is, tetramethoxysilane 3
4.2 g (0.25 mol), 44.2 (0.25 mol) of γ-mercaptopropyltrimethoxysilane and 36.5 g of methanol were weighed into a reaction vessel equipped with a cooler, and mixed and stirred well. Dissolve 0.9 ml of concentrated hydrochloric acid in water and add 1
40.5 g of the solution adjusted to 62 g was added, stirring was continued at 50 ° C. for 2 hours, and a solution dissolved in 3.6 g of triethanolamine and 18.0 g of methanol was added to gel the system. This gel was filtered, washed and dried to obtain the silicon compound 1 of the present invention. It was found from polynuclear nuclear magnetic resonance that this substance contained 0.45 sulfur atom per silicon atom.

Example 2 Egg albumin was added to 50 p.
p. m. 25 ml of an aqueous solution is adjusted to various pHs with 1N nitric acid or 1N sodium hydroxide.
g of silicon compound 1 was added, and the mixture was stirred at 20 ° C. for 24 hours.
As a control, water was added instead of the silicon compound 1, and silica gel was used as the comparative example 1 instead of the silicon compound 1. After completion of the stirring, the mixture was filtered, and an albumin test reagent ("Test Wako": manufactured by Wako Pure Chemical Industries, Ltd.) was added to the filtrate to form a color. The absorbance (680 nm) was measured. Divide by the absorbance of the example, multiply by 100,
It subtracted from 100, and was set as the adsorption rate. Table 1 shows the results. This indicates that the silicon compound of the present invention is excellent in adsorbing proteins and the like, and that the adsorption characteristics are changed by changing the pH. From this, it can be seen that adsorption-desorption can be controlled and can be a carrier such as a column.

[0016]

[Table 1]

Example 3 Silicon compound 2 of the present invention was obtained by replacing γ-mercaptopropyltrimethoxysilane of Example 1 with γ-mercaptopropyltriethoxysilane. The same study as in Example 2 was performed at pH 4, and as a result, excellent albumin adsorption ability was exhibited as in Silicon Compound 1.

Example 4 Silicon compound 3 of the present invention was obtained by changing γ-mercaptopropyltrimethoxysilane of Example 1 to dimethylmethyl-γ-mercaptopropylsilane. The same study as in Example 2 was performed at pH 4, and as a result, excellent albumin adsorption ability was exhibited as in Silicon Compound 1.

Example 5 Silicon compound 4 of the present invention was obtained by changing γ-mercaptopropyltrimethoxysilane of Example 1 to ethyldimethyl-γ-mercaptopropylsilane. The same study as in Example 2 was performed at pH 4, and as a result, excellent albumin adsorption ability was exhibited as in Silicon Compound 1.

Example 6 20 g of silica gel was coated with 5 g of dimethoxy-γ-mercaptopropylsilane chloride and heated at 130 ° C. for 48 hours under a nitrogen stream to obtain a silicon compound 5 of the present invention. The same study as in Example 2
As a result, the albumin adsorption ability was excellent as in the case of silicon compound 1.

Example 7 20 g of a cross-linked dimethylpolysiloxane (manufactured by Toray Co., Ltd .; "Trefil") was coated with 5 g of dimethoxy-γ-mercaptopropylsilane chloride, and heated at 130 ° C. for 48 hours in a nitrogen stream. Invented silicon compound 6 was obtained. The same study as in Example 2 was performed at pH 4, and as a result, excellent albumin adsorption ability was exhibited as in Silicon Compound 1.

Example 8 Methylsiloxane network polymer (manufactured by Toshiba Silicone Co., Ltd .; "Tospearl 120")
A ") 20 g of dimethoxy-γ-mercaptopropyl silane chloride was coated on 5 g, and 130 g of
It heated at 48 degreeC for 48 hours, and obtained the silicon compound 7 of this invention. The same study as in Example 2 was performed at pH 4, and as a result, excellent albumin adsorption ability was exhibited as in Silicon Compound 1.

[0023]

According to the present invention, novel adsorbents for amino acids, peptides, proteins and the like can be provided.

Claims (4)

[Claims] 1. A silicate compound having a partial structure represented by the following general formula (I). Embedded image Formula (I) (wherein, R1, R2, R3 and R4 each independently represent O-Si, OR5, R5, and R5 each independently represents a carbon atom which may have a hydrogen atom or a mercapto group. Represents an alkyl group of the formulas 1 to 4, and R1, R2, R3
Alternatively, at least one of R4 is an alkyl group having 1 to 4 carbon atoms having a mercapto group. ) 2. The method according to claim 1, wherein the material is a solid.
The silicon compound according to the above. 3. The silicon according to claim 1, which is obtained by condensation of a compound represented by the general formula (II) and a compound represented by the general formula (III). Compound. Embedded image Formula (II) (wherein, R1 ′, R2 ′, R3 ′ and R4 ′ each independently represent OH, a halogen atom, OR5 ′, R5 ′, and R5 ′ each independently represents a hydrogen atom or a mercapto group. Represents an alkyl group having 1 to 4 carbon atoms which may have the formula, and at least one of R 1 ′, R 2 ′, R 3 ′ or R 4 ′ is an alkyl group having 1 to 4 carbon atoms having a mercapto group. And at least one is an alkyloxy group having 1 to 4 carbon atoms or a halogen atom.) General formula (III) (wherein, R6, R7, R8 and R9 each independently represent OH, a halogen atom, O—R10 or R10, R10 represents an alkyl group having 1 to 4 carbon atoms or
At least two of 6, R7, R8, and R9 are a hydroxyl group, an alkyloxy group, or a halogen atom. ) 4. An adsorbent for an amino acid, a peptide or a protein comprising the silicon compound according to any one of claims 1 to 3.